Different protein turnover of interleukin‐6‐type cytokine signalling components
Open accessAbstract
Interleukin (IL)‐6 and IL‐6‐type cytokines signal through the gp130/Jak/STAT signal transduction pathway. The key components involved are the signal transducing receptor subunit gp130, the Janus kinases Jak1, Jak2 and Tyk2, STAT1 and STAT3 of the family of signal transducers and activators of transcription, the protein tyrosine phosphatase SHP2 and the suppressors of cytokine signalling SOCS1, SOCS2 and SOCS3. Whereas considerable information has been accumulated concerning the time‐course of activation for the individual signalling molecules, data on the availability of the proteins involved in IL‐6‐type cytokine signal transduction are scarce. Nevertheless, availability of these molecules, determined by the balance of protein synthesis and degradation, also influences IL‐6‐type cytokine signal transduction. Here, we present a comprehensive set of data on the half‐lives of the key molecules involved in the IL‐6 signal transduction pathway. The turnover rates for the various proteins differ substantially. Three groups of signalling proteins can be discriminated: whereas the feedback inhibitors SOCS1, SOCS2 and SOCS3 are very short‐lived, STAT1, STAT3 and SHP2 have an extremely slow turnover rate. Interestingly, the half‐life of STAT3β, a splice variant of STAT3α, is reduced to almost 50% of the half‐life of STAT3α. The Janus kinases Jak1, Jak2, Tyk2 and gp130 show intermediate half‐lives. Our data imply that signalling components activated by post‐translational modifications are long‐lived whereas the activity of very short‐lived proteins is regulated mainly at the transcriptional level.
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Depending on the tissue or cell type, the mRNA is short lived and the half-life of the SOCS protein is between 1 to 2 hours.
“Depending on the tissue or cell type, the mRNA is short lived and the half-life of the SOCS protein is between 1 to 2 hours (23).”
From Expression of suppressors of cytokine signaling during liver regeneration (2001) · cites this paper as [23]
The SOCS3 protein is highly labile.
“The kinetics of Socs3 mRNA and SOCS3 protein expression were similar, suggesting that the SOCS3 protein is highly labile, a finding that is consistent with the reported half-life of this protein (33).”
From The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling (2006) · cites this paper as [33]
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Principles of interleukin (IL)-6-type cytokine signalling and its regulation
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Expression of suppressors of cytokine signaling during liver regeneration
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- Authors
- Siewert, E., Müller‐Esterl, W., Starr, R., Heinrich, P. C., & Schaper, F.
- Affiliations
- RWTH Aachen University (DE)
- Johannes Gutenberg University Mainz (DE)
- The Royal Melbourne Hospital (AU)
- ORCID
- Schaper, Fred
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 1999-10
- Volume
- 265
- Issue
- 1
- Pages
- 251-257
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W2074478439
- Cited by
- 121
- References
- 6
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2022: 5 · 2021: 10 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 5 · 2015: 5 · 2013: 6 · 2012: 7
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- interleukin-6, gp130, JAK/STAT signaling, protein turnover, protein half-life, STAT3β, STAT1, SHP2, SOCS1, SOCS2, SOCS3, JAK1, JAK2, TYK2, suppressor of cytokine signaling, post-translational modification, transcriptional regulation
- MeSH terms
- DNA-Binding Proteins, Half-Life, Membrane Glycoproteins, Protein-Tyrosine Kinases, Recombinant Proteins, Signal Transduction, Trans-Activators, Antigens, CD, Interleukin-6, Cytokines, Protein Tyrosine Phosphatases, Intracellular Signaling Peptides and Proteins, STAT1 Transcription Factor, STAT2 Transcription Factor, Cytokine Receptor gp130, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatase, Non-Receptor Type 11
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